Control of Oligodendrocyte Precursor Proliferation Mediated by Density-Dependent Cell Cycle Protein Expression

The proliferation of oligodendrocyte precursors is closely regulated in the developing vertebrate CNS. In previous studies we have demonstrated a cell-type-specific density-dependent feedback mechanism that contributes to the control of oligodendrocyte progenitor cell clonal expansion in vitro. Here we demonstrate a density-dependent reduction in the proliferation of oligodendrocyte precursors. This inhibition of proliferation is correlated with increases in expression levels of the cell cycle inhibitor p27Kip1, reductions in the expression of cyclin A and changes in the relative phosphorylation levels of Rb. These changes are reversible on replating at low density suggesting that additional signals are required for terminal oligodendrocyte differentiation.